Nai-Wen Chi, MD, PhD

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My laboratory is interested in how insulin stimulates the uptake of glucose into myocytes and adipocytes. Insulin is known to achieve this by causing the glucose transporter GLUT4 to redistribute from intracellular vesicles to the cell surface, where GLUT4 can mediate glucose uptake. The precise regulatory mechanism of this process, however, remains unclear. We have found that GLUT4-containing vesicles interact with a molecular scaffold called tankyrase. Moreover, tankyrase has an unusual activity that can modify interacting partners through poly(ADP-ribosyl)ation, and this enzymatic activity is enhanced by insulin stimulation. We therefore hypothesized a role of this insulin-regulated activity of tankyrase in GLUT4 targeting. We are currently using molecular and cell-biology techniques to test this hypothesis. Our long-term goal is to identify the mechanism that couples the insulin signaling cascade with GLUT4 targeting machinery.